Endogenous opioids regulate moment-to-moment neuronal communication and excitability

Bryony L. Winters, Gabrielle C. Gregoriou, Sarah A. Kissiwaa, Oliver A. Wells, Danashi I. Medagoda, Sam M. Hermes, Neil T. Burford, Andrew Alt, Sue Aicher, Elena E. Bagley

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Fear and emotional learning are modulated by endogenous opioids but the cellular basis for this is unknown. The intercalated cells (ITCs) gate amygdala output and thus regulate the fear response. Here we find endogenous opioids are released by synaptic stimulation to act via two distinct mechanisms within the main ITC cluster. Endogenously released opioids inhibit glutamate release through the δ-opioid receptor (DOR), an effect potentiated by a DOR-positive allosteric modulator. Postsynaptically, the opioids activate a potassium conductance through the μ-opioid receptor (MOR), suggesting for the first time that endogenously released opioids directly regulate neuronal excitability. Ultrastructural localization of endogenous ligands support these functional findings. This study demonstrates a new role for endogenously released opioids as neuromodulators engaged by synaptic activity to regulate moment-to-moment neuronal communication and excitability. These distinct actions through MOR and DOR may underlie the opposing effect of these receptor systems on anxiety and fear.

Original languageEnglish (US)
Article number14611
JournalNature Communications
Volume8
DOIs
StatePublished - Mar 22 2017

Fingerprint

fear
Opioid Analgesics
communication
Communication
moments
anxiety
Fear
glutamates
Opioid Receptors
cells
stimulation
learning
modulators
potassium
ligands
output
Amygdala
Modulators
Neurotransmitter Agents
Glutamic Acid

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Winters, B. L., Gregoriou, G. C., Kissiwaa, S. A., Wells, O. A., Medagoda, D. I., Hermes, S. M., ... Bagley, E. E. (2017). Endogenous opioids regulate moment-to-moment neuronal communication and excitability. Nature Communications, 8, [14611]. https://doi.org/10.1038/ncomms14611

Endogenous opioids regulate moment-to-moment neuronal communication and excitability. / Winters, Bryony L.; Gregoriou, Gabrielle C.; Kissiwaa, Sarah A.; Wells, Oliver A.; Medagoda, Danashi I.; Hermes, Sam M.; Burford, Neil T.; Alt, Andrew; Aicher, Sue; Bagley, Elena E.

In: Nature Communications, Vol. 8, 14611, 22.03.2017.

Research output: Contribution to journalArticle

Winters, BL, Gregoriou, GC, Kissiwaa, SA, Wells, OA, Medagoda, DI, Hermes, SM, Burford, NT, Alt, A, Aicher, S & Bagley, EE 2017, 'Endogenous opioids regulate moment-to-moment neuronal communication and excitability', Nature Communications, vol. 8, 14611. https://doi.org/10.1038/ncomms14611
Winters BL, Gregoriou GC, Kissiwaa SA, Wells OA, Medagoda DI, Hermes SM et al. Endogenous opioids regulate moment-to-moment neuronal communication and excitability. Nature Communications. 2017 Mar 22;8. 14611. https://doi.org/10.1038/ncomms14611
Winters, Bryony L. ; Gregoriou, Gabrielle C. ; Kissiwaa, Sarah A. ; Wells, Oliver A. ; Medagoda, Danashi I. ; Hermes, Sam M. ; Burford, Neil T. ; Alt, Andrew ; Aicher, Sue ; Bagley, Elena E. / Endogenous opioids regulate moment-to-moment neuronal communication and excitability. In: Nature Communications. 2017 ; Vol. 8.
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